Betibeglogene autotemcel

SOMERVILLE, Mass.--( BUSINESS WIRE )--bluebird bio, Inc. (Nasdaq: BLUE) today announced updated data from patients with beta-thalassemia who require regular blood transfusions treated with betibeglogene autotemcel (beti-cel, approved commercially as ZYNTEGLO™) in clinical studies. The data was presented today at the 66 th American Society of Hematology (ASH) Annual Meeting and Exposition. “ Updated follow-up data of up to 10 years showed that patients treated with beti-cel in clinical trials experienced durable transfusion independence and normal or near-normal hemoglobin, regardless of genotype and age, and a continued favorable safety profile”, said Richard Colvin, M.D., Ph.D., chief medical officer, bluebird bio. “ We are deeply grateful for the ongoing commitment of our investigators, patients, and study participants. Our collective efforts are not only advancing the field of gene therapy but also providing new hope and possibilities for individuals with severe genetic diseases." “ Data at ASH demonstrate the durability of beti-cel through 10 years of long-term follow-up, giving additional confidence in that the transformational outcomes observed in parent studies are sustained over time,” said Alexis Thompson, MD, MPH, Chief of the Division of Hematology at Children’s Hospital of Philadelphia, which is a Qualified Treatment Center for ZYNTEGLO. “ These long-term data demonstrate beti-cel’s continued positive impact on iron management outcomes over time, which can help inform treatment decisions by clinicians who are now using this therapy in the real-world setting.” Betibeglogene Autotemcel (beti-cel) Gene Addition Therapy results in durable Hemoglobin A (HbA) Production with up to 10 Years of Follow-Up in Participants with Transfusion-Dependent β-Thalassemia (Poster #2194) Long-term outcomes with beti-cel in adult and pediatric patients with TDT were presented in a poster session. The data focused on 63 adult and pediatric study participants who had received beti-cel in a Phase 1/2 or Phase 3 study. Two participants had 10 years of follow-up, and 51 (81.0%) participants had 5 or more years of follow-up. Additionally, iron status was assessed in study participants who achieved TI and discontinued chelation therapy. Results showed that majority of participants treated with beti-cel achieved TI. All participants achieved platelet and neutrophil engraftment. Specific findings showed: Of 63 patients, 52 (90.2% in Phase 3 studies and 68.2% in Phase 1/2 studies) achieved TI. All except one patient maintained TI through last follow-up. The median weighted average hemoglobin during TI was 10.2 mg/dL for Phase 1/2 studies and 11.2 mg/dL for Phase 3 studies. Achievement and maintenance of TI and median weighted average hemoglobin were similar across ages and genotypes. Study participants treated with beti-cel who achieved and maintained TI demonstrated effective restoration of iron homeostasis over time and reduced iron management burden. Among participants who achieved TI, improvements in serum ferritin and liver iron concentration were sustained through month 60. 28/37 (75.7%) study participants who achieved TI in Phase 3 studies are no longer undergoing iron chelation therapy. Both adult and pediatric health-related quality of life scores (HRQoL) remained above the normative population mean up to 60 months. All 26 participants who achieved TI and completed a questionnaire reported an overall benefit with beti-cel. The safety profile was consistent with known side effects of hematopoietic stem cell collection and the busulfan conditioning regimen. None of the study participants had a fatal event. No beti-cel–related serious adverse events were reported more than 2 years after infusion through last follow-up. No malignancies, insertional oncogenesis or vector-derived replication-competent lentivirus were reported in any study participants. Beti-cel was approved by the FDA in August 2022 and is commercially available in the United States as ZYNTEGLO. About ZYNTEGLO® (betibeglogene autotemcel) or beti-cel ZYNTEGLO is a first-in-class, one-time ex-vivo LVV gene therapy approved for the treatment of beta-thalassemia in adult and pediatric patients who require regular red blood cell transfusions. ZYNTEGLO works by adding functional copies of a modified form of the beta-globin gene (β A-T87Q- globin gene) into a patient’s own hematopoietic (blood) stem and progenitor cells to enable the production of a modified functional adult hemoglobin (HbA T87Q ). Once a patient has the β A-T87Q- globin gene, they have the potential to increase ZYNTEGLO-derived adult hemoglobin (HbA T87Q ) and total hemoglobin to normal or near normal levels that can eliminate the need for regular red blood cell (RBC) transfusions. Indication ZYNTEGLO is indicated for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell (RBC) transfusions. Important Safety Information Delayed Platelet Engraftment Delayed platelet engraftment has been observed with ZYNTEGLO treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia; 15% of patients had ≥ Grade 3 decreased platelets on or after Day 100. Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise. Risk of Neutrophil Engraftment Failure There is a potential risk of neutrophil engraftment failure after treatment with ZYNTEGLO. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 500 cells/microliter obtained on different days by Day 43 after infusion of ZYNTEGLO. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with ZYNTEGLO, provide rescue treatment with the back-up collection of CD34+ cells. Risk of Insertional Oncogenesis There is a potential risk of LVV mediated insertional oncogenesis after treatment with ZYNTEGLO. Patients treated with ZYNTEGLO may develop hematologic malignancies and should be monitored lifelong. Monitor for hematologic malignancies with a complete blood count (with differential) at Month 6 and Month 12 and then at least annually for at least 15 years after treatment with ZYNTEGLO, and integration site analysis at Months 6, 12, and as warranted. In the event that a malignancy occurs, contact bluebird bio at 1 833-999-6378 for reporting and to obtain instructions on collection of samples for testing. Hypersensitivity Reactions Allergic reactions may occur with the infusion of ZYNTEGLO. The dimethyl sulfoxide (DMSO) in ZYNTEGLO may cause hypersensitivity reactions, including anaphylaxis. Anti-retroviral and Hydroxyurea Use Patients should not take prophylactic HIV anti-retroviral medications or hydroxyurea for at least one month prior to mobilization, or for the expected duration for elimination of the medications, and until all cycles of apheresis are completed. If a patient requires anti-retrovirals for HIV prophylaxis, then confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells. Interference with Serology Testing Patients who have received ZYNTEGLO are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a false-positive test for HIV. Therefore, patients who have received ZYNTEGLO should not be screened for HIV infection using a PCR‑based assay. Adverse Reactions The most common non-laboratory adverse reactions (≥20%) were mucositis, febrile neutropenia, vomiting, pyrexia, alopecia, epistaxis, abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and pruritus. The most common Grade 3 or 4 laboratory abnormalities (>50%) include neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia. Drug Interactions Drug-drug interactions between iron chelators and the myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. The prescribing information for the iron chelator(s) and the myeloablative conditioning agent should be consulted for the recommendations regarding co-administration with CYP3A substrates. Some iron chelators are myelosuppressive. After ZYNTEGLO infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate. Pregnancy/Lactation Advise patients of the risks associated with conditioning agents, including on pregnancy and fertility. ZYNTEGLO should not be administered to women who are pregnant, and pregnancy after ZYNTEGLO infusion should be discussed with the treating physician. ZYNTEGLO is not recommended for women who are breastfeeding, and breastfeeding after ZYNTEGLO infusion should be discussed with the treating physician. Females and Males of Reproductive Potential A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before ZYNTEGLO administration. Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of ZYNTEGLO. Advise patients of the option to cryopreserve semen or ova before treatment if appropriate. Please see full Prescribing Information for ZYNTEGLO . About bluebird bio, Inc. bluebird bio is pursuing curative gene therapies to give patients and their families more bluebird days. Founded in 2010, bluebird has been setting the standard for gene therapy for more than a decade—first as a scientific pioneer and now as a commercial leader. bluebird has an unrivaled track record in bringing the promise of gene therapy out of clinical studies and into the real-world setting, having secured FDA approvals for three therapies in under two years. Today, we are proving and scaling the commercial model for gene therapy and delivering innovative solutions for access to patients, providers, and payers. With a dedicated focus on severe genetic diseases, bluebird has the largest and deepest ex-vivo gene therapy data set in the field, with industry-leading programs for sickle cell disease, β-thalassemia and cerebral adrenoleukodystrophy. We custom design each of our therapies to address the underlying cause of disease and have developed in-depth and effective analytical methods to understand the safety of our lentiviral vector technologies and drive the field of gene therapy forward. bluebird continues to forge new paths as a standalone commercial gene therapy company, combining our real-world experience with a deep commitment to patient communities and a people-centric culture that attracts and grows a diverse flock of dedicated birds. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements, such as statements regarding the therapeutic potential of ZYNTEGLO. Such forward-looking statements are based on historical performance and current expectations and projections about bluebird’s future goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond bluebird’s control and could cause bluebird’s future goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect bluebird bio’s business, particularly those identified in the risk factors discussion in bluebird bio’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by its subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the SEC. These risks and uncertainties include, but are not limited to: the risk that the efficacy and safety results from bluebird’s prior and ongoing clinical trials will not continue or be seen in the commercial context; the risk that there is not sufficient patient demand or payer reimbursement to support continued commercialization of ZYNTEGLO; the risk of insertional oncogenic or other safety events associated with lentiviral vector, drug product, or myeloablation, including the risk of hematologic malignancy; and the risk that bluebird’s products, including ZYNTEGLO, will not be successfully commercialized. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, bluebird bio undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

氨基观察-创新药组原创出品 作者 | 黄恺 "氨基一周"致力于提供"全球最重要的大健康产业新闻分析"，深入挖掘行业动态，洞察市场趋势。 无论您是行业从业者还是对大健康产业感兴趣的读者，"氨基一周"都将是您了解行业脉动的得力助手。欢迎关注我们，一起探索大健康产业的无限可能。 本周，"氨基一周"带来的产业动态分析要点包括： 恒瑞医药IL-17A单抗降价57% 带状疱疹疫苗遇冷 心脉医疗补税数千万 局限期小细胞肺癌迎四十年重大突破 TCE 前列腺癌预期再升温 美国开展天价药支付新尝试 / 01 / 恒瑞医药IL-17A单抗降价57% 上市仅3个月，恒瑞医药的IL-17A单抗夫那奇珠就降价了。 12月2日，江苏省公共资源交易中心发布公告称，对部分药品的挂网价格进行了调整，其中夫那奇珠单抗的售价从每支1986元降至860元，降幅超过56%。 由于夫那奇珠单抗上市仅3个月，恒瑞医药就选择降价，这种情况并不多见。当然，也可以理解，因为夫那奇珠在8月份获批，未能赶上今年的医保谈判，面临的压力不小。 在中国，司库奇尤单抗是最积极拥抱医保谈判的创新药物之一，其接连降价，打破了自免药物市场的局限。今年5月份，诺华表示，司库奇尤单抗已经覆盖超过国内50万患者，过去一年新增了20万患者，因此被誉为国内自免市场的奇迹。 在这一逻辑下，作为后来者的国产创新药，要想突围无疑需要在价格方面想办法。恒瑞医药的主动降价，也可以视为一种被动应对。 这不仅是IL-17A单抗领域上演的故事。在国内自免市场，进口药物基本都选择拥抱医保进行卡位，因此要想上演国产替代的故事，可能需要国内药企在商业化策略方面更进一步。 / 02 / 带状疱疹疫苗遇冷 国产替代的逻辑不好讲，海外重磅产品在国内复刻的轨迹也是一样。 带状疱疹疫苗被称之为老年人的HPV疫苗，葛兰素史克的带状疱疹疫苗Shingrix（欣安立适）以97.2%的保护率，被视作该领域“天花板”般的存在，因此成为过去几年涌现的新疫苗大单品。 国内这一市场究竟如何？智飞生物曾经抱有极高的期待。 去年10月份，双方协议约定，智飞生物2024年、2025年、2026年带状疱疹疫苗的最低年度采购金额分别是34.40亿元、68.80亿元、103.20亿元。 不过，目前来看这个目标的实现并不容易。 12月5日，智飞生物发布了关于与GSK优化并调整战略合作的公告，智飞生物代理GSK的重组带状疱疹疫苗的权利期限，从2026年底延长至2034年底，预计采购金额约为216亿元，具体采购情况将根据市场预期需求进行调整。 也就是说，Shingrix的放量可能不及预期。可能有竞争的因素，比如百克生物的减毒带状疱疹疫苗，虽然保护效率不高，但胜在价格更便宜。当然，这也与Shingrix自身价格相对较高有关。 不管怎么说，目前来看，因为多种因素限制，带状疱疹疫苗在国内市场的上限如何，还需要继续观察。 / 03 / 心脉医疗补税数千万 决定一家企业上限的，不仅是管线，还包括管理能力。心脉医疗要为自己的低级错误买单了。 由于被取消高新技术企业资格，心脉医疗需补缴税款及滞纳金合计约6000万—7000万元。这大约是公司去年扣非净利润的14%，显然，这会对其今年业绩造成影响。 更让投资者无法接受的，这本是一场不该出现的疏忽。因为公司被取消高新技术企业资格，是由于连续两年忘记填报企业发展情况报表。 有市场人士指出，这个报表并不繁琐，在监管指定的网站线上填写提交公司相关信息即可，这么简单的事情，心脉医疗为何连续两年都没有做？ 尽管心脉医疗已经着手补救，公司位列2024年第二批拟认定高新技术企业名单，但是7000万元左右的损失无法追回。这一事件更是影响了市场信心，因为这暴露了公司内控管理之混乱。 核心在于，无论从专利、研发成果还是营收、研发费用各方面来看，心脉医疗拿下高新技术企业资格都不在话下，这对于企业经营的好处也很多，最直接的就是税收优惠。然而，公司却因为忘记填表申报而被取消资格。 这些看似内部的疏忽因素，最终都将直接影响到企业在经营及资本市场上的表现和评价。而这提醒着包括心脉医疗在内的所有企业： 在追求技术革新与市场扩张的同时，更需谨慎地维护好公司的治理结构与管理，真正做到大而不乱。 更详细内容，可点击《揭开明星械企“管理能力”的盖子》 / 04 / 局限期小细胞肺癌迎四十年重大突破 局限期小细胞肺癌迎来重大进展。 12月4日，美国FDA批准了阿斯利康的PD-L1抑制剂度伐利尤单抗，用于治疗在接受同步含铂化疗和放疗后疾病未进展的局限期小细胞肺癌成人患者。 这是40年来局限期小细胞肺癌治疗的突破。 根据疾病发展阶段，小细胞肺癌可以分为局限期（LS-SCLC）和广泛期（ES-SCLC）两个阶段，分别约占小细胞肺癌的1/3和2/3。 对于局限期小细胞肺癌，目前的首选一线治疗方法仍然是放化疗，尤其是顺铂联合依托泊苷的治疗方案，这一组合在治疗中占据着绝对主导地位。 因此，市场对于度伐利尤单抗的上市抱有较高的关注度。这也反映了一个事实，小细胞肺癌的治疗攻坚正在加速。 未来，随着新靶点、新技术的涌现，SCLC的临床选择更多，是值得期待的，这其中可能也会出现诸多销售额可观的药物。 / 05 / TCE 前列腺癌预期再升温 攻克小细胞癌的TCE，如今在前列腺癌领域预期再升温。 日前，Janux公布了PSMA/CD3双抗JANX007的最新研究进展。 截至2024年11月15日，16名前接受过诺华Pluvicto治疗的患者每周接受一次JANX007，目标剂量范围为2 mg至9 mg。 所有剂量组，均观察到高前列腺特异性抗原（PSA）反应率和深度PSA下降。具体来看，100%的患者达到最佳PSA50下降，63%的患者达到最佳PSA90下降，31%的患者达到最佳PSA99下降。 并且持久性数据也是非常不错，在目标剂量≥2 mg的患者中，75%的患者在≥12周时维持PSA50下降，50%的患者在≥12周时维持PSA90下降。 另外，无论耐药驱动异常状态如何，或之前是否接受过紫杉烷或ARPi治疗，均观察到深度和持久的PSA反应。 PSA50指标能否转化为生存期获益尚不得而知，但对于早期临床管线项目是一个重要的疗效提示信号。对比来看，JANX007在5线疗法展示出的PSA降低和药效的持久性，甚至优于目前临床上的2线疗法。 也正因此，Janux在公布数据后，当天股价涨幅接近50%，上演了暴力奇迹。这也会进一步催生TCE技术的热潮。 / 06 / 美国开展天价药支付新尝试 对于天价药，美国医保正在尝试新的支付模式。 日前，Bluebird和Vertex/CRISPR的SCD基因疗法与美国CMS（美国联邦医疗保险和医疗补助服务中心）正式达成了“按结果付费”的协议，并将于明年1月推出新的支付模式。 根据CMS，这项计划是通过基于结果的协议（OBA）向制造商支付款项，而支付金额与一定时间内患者的健康结果挂钩，同时CMS也希望与药品销量挂钩。其核心有三： 在该模型下，如果基因治疗在长期改善健康结果方面的成功率低于预期，药物制造商将向医疗支付方退还部分治疗费用。协议还将包括其他价格让步，如基于数量的回扣或保证回扣。 CMS将代表各州与制造商就为Medicaid为主要支付方的受益人提供的细胞和基因治疗进行谈判。该模型允许CMS将各州聚集在一起，进行多州基础上的谈判，而不是每个州都与制造商建立自己的OBA。 CMS还将负责建立财务和临床结果衡量标准、协调数据和评估结果。各州仍将负责支付细胞和基因治疗的费用，但价格回扣将根据CMS谈判的特定结果而确定。 这些组合模式不仅可以降低患者和保险提供者的经济风险，还能激励制药企业和医疗服务提供者不断优化和改进治疗方案。 同时，CMS还表示，随着效果显现，后续还将对更多细胞和基因治疗药物采用这种付费模式。 基因疗法同时也是天价疗法的代名词。上述两款基因疗法的定价分别为220万美元（Zynteglo）和310万美元（Skysona），价格极高。 因此，如果新模式能够成功实施，对于天价疗法可能是个好消息。 更详细内容，可点击《破解天价药支付难题，美国医保打了个样》 PS：欢迎扫描下方二维码，添加氨基君微信号交流。